| Identification | Back Directory | [Name]
GNF5 | [CAS]
778277-15-9 | [Synonyms]
GNF5
GNF-5
GNF 5
CS-1437
GNF 5; GNF5
GNF-5, >=98%
GNF5 USP/EP/BP
GNF-5 , 778277-15-9
6-ISOPROPOXY-1,3-BENZOTHIAZOL-2-AMINE
ert-butyl 2-oxopiperidine-1-carboxylate
N-(2-Hydroxyethyl)-3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]benzamide
Benzamide, N-(2-hydroxyethyl)-3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]-
N-(2-Hydroxyethyl)-3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]benzamide GNF-5
GNF 5 N-(2-Hydroxyethyl)-3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]benzamide | [EINECS(EC#)]
200-256-5 | [Molecular Formula]
C20H17F3N4O3 | [MDL Number]
MFCD16877246 | [MOL File]
778277-15-9.mol | [Molecular Weight]
418.369 |
| Chemical Properties | Back Directory | [Boiling point ]
612.4±55.0 °C(Predicted) | [density ]
1.385±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: soluble10mg/mL (clear solution) | [form ]
powder | [pka]
13.36±0.46(Predicted) | [color ]
white to beige | [InChI]
1S/C20H17F3N4O3/c21-20(22,23)30-16-6-4-15(5-7-16)27-18-11-17(25-12-26-18)13-2-1-3-14(10-13)19(29)24-8-9-28/h1-7,10-12,28H,8-9H2,(H,24,29)(H,25,26,27) | [InChIKey]
IIQUYGWWHIHOCF-UHFFFAOYSA-N | [SMILES]
OCCNC(=O)c1cccc(c1)-c2cc(Nc3ccc(OC(F)(F)F)cc3)ncn2 |
| Hazard Information | Back Directory | [Uses]
GNF-5 is a selective and allosteric Bcr-Abl inhibitor. It is a COVID19-related research product. | [Biological Activity]
gnf-5 is an analogue of gnf-2 and a selective non-atp competitive inhibitor of bcr-abl with an ic50 value of 0.1 to >10 μm in various cancer cell lines.bcr-abl is a fusion gene that results from the head-to-tail fusion of the bcr and abl genes[1]. bcr-abl upregulates production of tyrosine kinase and plays a central role in the pathogenesis of chronic myelogenous leukemia (cml) [1].gnf-5 has the same chemical structure as its parent molecule (gnf-2) with the exception of n-hydroxyethyl carboxamide at its 4-position and such modification provided gnf-5 a longer half-life from (2.30 hrs)[2]. similar with gnf-2, gnf-5 allosterically inhibits the proliferation of bcr-abl positive cell by binding to the myristate-binding site of abl and induces cell apoptosis[3]. in steady-state kinetic analyses, gnf-5 was able to inhibit wild type abl with an ic50 value of 0.22 μm[2]. in addition, gnf-5 also has a similar effectiveness against various imatinib? resistance cell lines: in e255v and t315i mutant ba/f3 cells, a 12-day incubation of gnf-5 2 was able to inhibit the proliferation of cells with a ic50 value of 0.38 and 5 μm, respectively[2].in mice injected with wild-type bcr-abl and luciferase expressing ba/f3 cells, continuous injection of gnf-5 for 7 days (50 mg/kg, twice per day) normalized peripheral blood cell counts, as well as spleen size[2]. when treating mice that injected with imatinib? resistance t315i bcr–abl-transduced bone marrow, daily injection of gnf-5 (75 mg/ kg, twice per day) significantly extended the survival day of mice from 24 days to 22 days[2]. | [in vivo]
GNF-5 (5 mg/kg iv. or 20 mg/kg oral) has suitable pharmacokinetic parameters[1].
GNF-5 (oral, 50 or 100 mg/kg, twice daily, for 7 days) shows efficacious in vivo but can observe relapses[1].
GNF-5 (75 mg/kg, b.i.d) inhibits T315I Bcr-Abl combination with nilotinib in vivo[1]. | Animal Model: | Male Balb/c mice[1] | | Dosage: | 5 mg/kg, 20 mg/kg | | Administration: | 5 mg/kg intravenously or 20 mg/kg orally | | Result: | | AUC_inf (min*ug/mL) | 292.37 | | AUC_inf (hrs*nM | 11647 | | Cmax(nM) | 4386.08 | | Tmax(hrs) | 0.50 | | Clast (nM) | 636.16 | | T1/2(hrs) | 2.30 | | Vss(L/kg) | 9.18 | | F (%) | 44.82 | |
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| Animal Model: | p210 xenograft model[1] | | Dosage: | 50 or 100 mg/kg | | Administration: | oral, twice daily, for 7 days | | Result: | Could normalize blood counts and spleen size. |
| Animal Model: | Bone marrow transduction/transplantation model[1] | | Dosage: | 75 mg/kg | | Administration: | twice daily | | Result: | Showed no significant response (alone).
Showed no toxicity and had a strong and sustained inhibition of Bcr-Abl-mediated signaling combination with nilotinib.
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| [storage]
Store at +4°C | [References]
[1]. rumpold, h. & webersinke, g. 2011. molecular pathogenesis of philadelphia-positive chronic myeloid leukemia - is it all bcr-abl? curr cancer drug targets, 11, 3-19.
[2]. zhang, j., adrian, f. j., jahnke, w., et al. 2010. targeting bcr-abl by combining allosteric with atp-binding-site inhibitors. nature, 463, 501-506.
[3]. karunakaran, u., park, s. j., jun, d. y., et al. non-receptor tyrosine kinase inhibitors enhances β-cell survival by suppressing the pkcδ signal transduction pathway in streptozotocin – induced β-cell apoptosis. cellular signalling. |
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